The P body protein LSm1 contributes to stimulation of hepatitis C virus translation, but not replication, by microRNA-122.
The P body protein LSm1 contributes to stimulation of hepatitis C virus translation, but not replication, by microRNA-122.
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DOI：
10.1093/nar/gkt941
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发表时间：
2014-01
影响因子：
14.9
通讯作者：
Jopling CL
中科院分区：
文献类型：
--
作者：
Roberts AP;Doidge R;Tarr AW;Jopling CL
P体蛋白LSm 1刺激丙型肝炎病毒（HCV）的翻译和复制。由于肝脏特异性microRNA-122（miR-122）是HCV复制所必需的，并且与P体相关，我们研究了LSm 1对HCV的调控是否涉及miR-122。在这里，我们证明LSm 1有助于激活miR-122驱动的HCV内部核糖体进入位点（IRES）翻译。LSm 1的这种作用是专门针对miR-122翻译激活的，因为LSm 1缺失不会影响miR-122在3′非翻译区（UTR）位点的抑制功能，也不会影响miR-122在完全互补位点介导的切割。我们发现LSm 1并不影响microRNA（miRNA）诱导的沉默复合物向HCV 5′UTR的募集，这意味着它在靶结合后调节miR-122的功能。与miR-122和LSm 1在翻译中的相互作用相反，我们发现LSm 1不是miR-122刺激HCV复制所必需的，这表明miR-122调节HCV翻译和复制有不同的要求。这是第一次，我们已经确定了一种蛋白质因子，它特异性地促进miR-122激活HCV IRES驱动的翻译，但不影响miRNA的其他活性。我们的研究结果增强了对miR-122和LSm 1调节HCV的机制的理解。
The P body protein LSm1 stimulates translation and replication of hepatitis C virus (HCV). As the liver-specific microRNA-122 (miR-122) is required for HCV replication and is associated with P bodies, we investigated whether regulation of HCV by LSm1 involves miR-122. Here, we demonstrate that LSm1 contributes to activation of HCV internal ribosome entry site (IRES)-driven translation by miR-122. This role for LSm1 is specialized for miR-122 translation activation, as LSm1 depletion does not affect the repressive function of miR-122 at 3′ untranslated region (UTR) sites, or miR-122–mediated cleavage at a perfectly complementary site. We find that LSm1 does not influence recruitment of the microRNA (miRNA)-induced silencing complex to the HCV 5′UTR, implying that it regulates miR-122 function subsequent to target binding. In contrast to the interplay between miR-122 and LSm1 in translation, we find that LSm1 is not required for miR-122 to stimulate HCV replication, suggesting that miR-122 regulation of HCV translation and replication have different requirements. For the first time, we have identified a protein factor that specifically contributes to activation of HCV IRES-driven translation by miR-122, but not to other activities of the miRNA. Our results enhance understanding of the mechanisms by which miR-122 and LSm1 regulate HCV.
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影响因子：
56.9
作者：
Jopling, CL;Yi, MK;Sarnow, P
通讯作者：
Sarnow, P
DOI：
10.1126/science.1187197
发表时间：
2010-06-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cazalla D;Yario T;Steitz JA
通讯作者：
Steitz JA
DOI：
10.1073/pnas.1213515110
发表时间：
2013-01-29
影响因子：
11.1
作者：
Li, You;Masaki, Takahiro;Lemon, Stanley M.
通讯作者：
Lemon, Stanley M.
影响因子：
3.7
作者：
Huys A;Thibault PA;Wilson JA
通讯作者：
Wilson JA
影响因子：
16
作者：
Arribere, Joshua A.;Doudna, Jennifer A.;Gilbert, Wendy V.
通讯作者：
Gilbert, Wendy V.